WHO Prequalification of In Vitro Diagnostics PUBLIC REPORT. Product: OraQuick HIV 1/2 Rapid Antibody Test WHO reference number: PQDx

Transcription

1 WHO Prequalification of In Vitro Diagnostics PUBLIC REPORT Product: OraQuick HIV 1/2 Rapid Antibody Test WHO reference number: PQDx OraQuick HIV 1/2 Rapid Antibody Test with product codes 5x and 5x4-0012, manufactured in Thailand for OraSure Technologies, Inc., rest-of-world regulatory version, was accepted for the WHO list of prequalified in vitro diagnostics and was listed on 8 April This public report was amended on 14 June 2016, and then further amended on 2 February Intended use: OraQuick HIV-1/2 Rapid Antibody Test is a qualitative, in vitro immunoassay. It detects antibodies to the human immunodeficiency virus types 1 and 2 (HIV-1/2) in human oral fluid, whole blood, serum or plasma. The assay is read visually, and is intended for the detection of such antibodies from individuals infected by HIV-1 or HIV-2. Assay description: OraQuick HIV-1/2 is a visually read, qualitative immunochromatographic test for the detection of antibodies to HIV-1 and HIV-2. The flat pad that contacts the gums is treated with a mild surfactant, and no materials of viral origin are used in the manufacture of the test. One cannot become infected with HIV by taking this test. The device is placed into the subject s mouth, so that the flat pad is between the cheek and the outer gums, then swabbed across the outer gum line. The device is then placed into a vial containing a premeasured amount of developer solution, and allowed to develop. The stand provided to hold the developer vial must be used. Fluid from the surface of the gums enters the device through the flat pad, then flows onto a test strip. As it migrates across the strip, it hydrates and mixes with a red-colored reagent (protein A bound to colloidal gold). IgG antibodies in the specimen bind to the reagent. If in turn the bound IgG antibody recognizes synthetic HIV-1 or HIV-2 antigen immobilized on the strip enclosed in the housing, a colored line forms in the T (test) area of the result window. If not, no line forms there. Further up the strip, the colored reagent encounters an immobilized biochemical that recognizes human antibodies. The line that forms in this C area of the result window is the control line. It demonstrates assay validity, indicating that the oral fluid contains IgG, that the strip is functioning properly, and that fluid is migrating appropriately through the device. Alternatively, a capillary or venous whole blood, serum or plasma specimen can be collected using the loop provided. The loop is immersed into the developer and stirred to Page 1 of 20

2 mix. Kit controls for OraQuick HIV-1/2 Rapid Antibody Test are available separately. These serve to demonstrate that the test is maintaining adequate performance. Test kit contents: Component Pouch containing 1 test device, 1 desiccant, 1 developer solution vial containing 1ml of phosphate buffer saline solution containing polymers and an antimicrobial agent. 100 tests (product code 5x4-0010) Test stands Specimen collection loops, 5µl 5 25 Instructions for use tests (product code 5x4-0012) Test kit controls contents: Item OraQuick ADVANCE Rapid HIV-1/2 Antibody Test Kit Controls 3 Vials Vial 1-1x HIV-1 positive control; Vial 2-1x HIV-2 positive control; and Vial 3-1x Negative control. Sufficient to run approximately 25 tests. Unopened expiry date: 12-months Opened expiry date: 8-weeks when stored at 2 8 C). Product code Items required but not provided: Item Consumables, for testing on fingerstick whole blood specimen Equipment Description Alcohol swabs Sterile lancets Timer or watch Storage: The test kit should be stored at 2 to 30 C. Store unused tests unopened at 2-30 ºC. Do not open the foil pouch until you are ready to perform a test. This test should be performed at temperatures in the range of (15-37 C). If stored refrigerated, ensure that the Divided Pouch is brought to operating temperature (15-37 C) before performing testing. Page 2 of 20

3 If the test kit is stored at temperatures outside of ambient temperature (2-27 C), or used outside of the operating temperature (15-37 C), use the Kit Controls to ensure performance of the test. Shelf-life upon manufacture: 30 months. Warnings: Handle specimens and materials contacting specimens as if potentially infectious biological materials in accordance with Universal Precautions. It has been reported that infectious HIV can be isolated from the oral fluid of some HIV infected individuals. When detectable in oral fluid, infectious virus is present at low levels compared with blood and may be inactivated by salivary inhibitors. Clean and disinfect any oral fluid- or blood-containing spills. Use a 0.5% sodium hypochlorite (1:10 household bleach) solution, or other appropriate disinfectant. Dispose of all potentially contaminated materials in accordance with local regulations for disposal of biohazardous materials. If an oral fluid test must be repeated (following the gum-swab procedure), wait 15 minutes and start the process over using a new test device, and use the whole blood test procedure. Use adequate lighting to visually check a test result. If two lines are present at any visible intensity, the test result is interpreted as reactive. Do not cover or otherwise obstruct the two small holes on the back of the test device. The flow of fluid can be impaired. Individuals infected with HIV-1 and/or HIV-2 who are receiving antiretroviral therapy (ART) may produce false negative results. Individuals undergoing preventive treatment for HIV may produce false negative results. Do not use the test beyond the expiration date printed on the Divided Pouch. Always check expiration date prior to testing. Limitations 1. The OraQuick HIV-1/2 Rapid Antibody Test must be used in accordance with these instructions to obtain an accurate result. 2. Oral fluid specimens for testing must be freshly collected, as detailed in the procedure. For blood-based testing, aged specimens or specimens which have undergone repeated freeze-thaw cycles may give incorrect results. 3. Blood-based specimens that have been heat or chemically inactivated may not give accurate results. 4. The test is not for use with body fluids not specified here, with oral fluid collected by other methods or with other commercially available oral fluid collectors, or with pooled specimens. Page 3 of 20

4 5. Clinical data has not been collected to demonstrate the performance of OraQuick HIV-1/2 Rapid Antibody Test in persons under 13 years of age. 6. Do not use this test as the sole basis for a diagnosis of AIDS, ARC or HIV infection. Any reactive result should be confirmed. 7. For a reactive result, the intensity of the test line does not necessarily correlate to the titer of antibody in the specimen. 8. A non-reactive result does not preclude the possibility of exposure to HIV or infection by HIV. An antibody response to recent exposure may take some time to reach detectable levels. 9. If a red background in the result window makes it difficult to read the test at 20 minutes, wait until the background clears to read the result (but not more than 40 minutes total time). Summary of WHO prequalification assessment for OraQuick HIV 1/2 Rapid Antibody Test Date Outcome PQ amended 14 June 2016, listed 2 February 2017 PQ listing 8 April 2016 listed Dossier review 26 January 2016 MR Site inspection(s) of quality management system 8 January 2016 MR Laboratory evaluation of performance and operational characteristics 28 January 2016 MR MR: Meets requirements N/A: Not applicable Prioritization for prequalification Based on the established criteria, OraQuick HIV 1/2 Rapid Antibody Test was given priority for WHO prequalification. Product dossier assessment The Manufacturer submitted a product dossier for OraQuick HIV 1/2 Rapid Antibody Test as per the Instructions for compilation of a product dossier (PQDx_018 v1). The information (data and documentation) submitted in the product dossier was reviewed by WHO staff and external technical experts (assessors) appointed by WHO. The manufacturer's responses to the nonconformities found during dossier screening and assessment findings were accepted on 26 January Based on the product dossier screening and assessment findings, the product dossier for OraQuick HIV 1/2 Rapid Antibody Test meets WHO prequalification requirements. Page 4 of 20

5 Manufacturing site inspection A comprehensive inspection was performed at the site of manufacture (220 East First Street, Bethlehem, PA, , USA) of OraQuick HIV 1/2 Rapid Antibody Test, on 3-5 November 2014 as per the Information for manufacturers on prequalification inspection procedures for the sites of manufacture of diagnostics (PQDx_014 v1). In addition, an inspection was undertaken at a key supplier (Pacific Biotech, 42M004 Phetchabun Chalianglub Rd., Napa, Muang, Petchabun 6700, Thailand). The inspections found that the manufacturer had an acceptable quality management system and good manufacturing practices in place that ensured the consistent manufacture of a product of good quality. The manufacturer s response to the nonconformities found at the time of the inspection were accepted on 8 January Based on the site inspections and corrective action plan review, the quality management system for OraQuick HIV 1/2 Rapid Antibody Test meets WHO prequalification requirements. Laboratory evaluation OraQuick HIV-1/2 Rapid Antibody Test was evaluated by WHO in 2014 on serum/plasma specimens and in 2015 for oral fluid specimens. From this evaluation, we drew the following conclusions: OraQuick HIV-1/2 Rapid Antibody Test is a qualitative rapid immunochromatographic test for the detection of antibodies to HIV 1/2 in oral fluid, whole blood, serum or plasma specimens. This type of assay requires no sophisticated equipment and can therefore be performed in laboratories with limited facilities and non-laboratory settings. Reading of the results can be done visually i.e. subjectively read. Performance characteristics in comparison with an agreed reference standard: serum/plasma specimens (N=1118) Initial (95% CI) Final (95% CI) Sensitivity % 99.1% (97.8% %) 99.1% (97.8% %) Specificity % 99.8% (99.2% - 100%) 99.8% (99.2% - 100%) Invalid rate % 0.1% Inter-reader variability % 0% Page 5 of 20

6 Performance characteristics in comparison with an agreed reference standard: oral fluid specimens (N=596) Initial (95% CI) Final (95% CI) Sensitivity % *99.1% (94.8% - 100%) Repeat testing was not conducted Specificity % 100% (99.0% - 100%) Repeat testing was not conducted Invalid rate % 0.1% Inter-reader variability % 0.4% *For patients not on antiretroviral therapy (ART) The instructions for use includes a warnings that individuals infected with HIV-1 and/or HIV-2 who are receiving antiretroviral therapy (ART) may produce false negative results and individuals undergoing preventive treatment for HIV may produce false negative results. Additional performance characteristics for serum/plasma evaluation Sensitivity during seroconversion on 8 seroconversion panels in comparison with a benchmark assay; Enzygnost Anti-HIV 1/2 Plus (Siemens Healthcare Diagnostics) Analytical sensitivity on a mixed titer panel in comparison with an agreed reference standard Lot to lot variation on a dilution panel Seroconversion sensitivity index of , therefore detection is later than the benchmark assay. 24 of 25 specimens were correctly classified. Acceptable Key operational characteristics Validated specimen types Number of steps Time to result Endpoint stability Internal QC In-use stability of reagents Serum, plasma (EDTA), venous whole blood (EDTA, Sodium heparin and sodium citrate), capillary whole blood, oral fluid 2, without precision required. 20 minutes 20 minutes (no more than 40 minutes after specimen added to developer vial) Yes, internal quality control in form of control line for detection of IgG. The foil pouch should be opened just before use. Page 6 of 20

7 Change notification In 2016, OraSure Technologies, Inc., submitted a change notification related changes made to changes to various raw materials, production and quality control processes. This change notification was assessed and product was found to meet WHO prequalification requirements. Page 7 of 20

8 Labelling 1. Labels 2. Instructions for use Page 8 of 20

9 Page 9 of 20

10 Page 10 of 20

11 Page 11 of 20

12 Page 12 of 20

13 Page 13 of 20

14 Page 14 of 20

15 Page 15 of 20

16 Page 16 of 20

17 Page 17 of 20

18 Page 18 of 20

19 Page 19 of 20

20 Page 20 of 20